The american cancer society estimates that there will be more than 15.5 million cancer survivors, 1.7 million new cancer patients, and 601,000 cancer deaths in the United States in 2017.¹ The number of cancer survivors is expected to grow to more than 20 million by the year 2026² (Fig. 98–1). It has been demonstrated that 40% to 60% of these survivors report one or more long-term functional deficits, with even higher rates for those with metastatic disease. This represents a massive population of patients with functional and quality of life limiting impairments. Unfortunately, many survivors accept their limitations as the “new normal.” Education of the rehabilitation professional is essential if we are to meet the needs of this critically underserved population.^3,4

Although there are numerous complications of cancer and cancer treatments, the focus of the chapter will be to provide an overview of key topics. Many cancer survivors will likely have multiple impairments that can be complex and interrelated. The complexity of such patients can be daunting for many rehabilitation professionals. While it may seem intimidating at times, it is important to remember that the physiatrist already has much of the knowledge and skills needed to care for the rehabilitation needs of this population. The approach to these patients is always to apply what one has learned through their training in the various domains of rehabilitation medicine, such as brain injury, stroke, musculoskeletal medicine, and spinal cord injury, and apply those to best improve the function and quality of life of the cancer patient.

Additionally, it is important to understand that in oncology every decision must be made using a careful cost/benefit analysis. Poor outcomes are common in cancer patients, despite one’s skill and intentions. The challenge for the physiatrist is to maximize function and quality of life while minimizing, to the best of their ability and knowledge, any potential adverse outcomes. Toward that goal, many of the most common and important concepts seen in cancer rehabilitation will be described here.

Direct Effects of Cancer

The direct effects of cancer itself are often secondary to the mass effect of the primary tumor or metastatic lesion. The clinical impact in this case would be dependent on the location and size of the disease often with clinically obvious effects. Examples would include a large lung tumor resulting in pulmonary dysfunction, metastasis to lymph nodes resulting in lymphedema, or a lesion in the epidural space resulting in spinal cord compromise. In addition, there are several unique instances in which knowledge of cancer’s direct effects must be recognized. These include effects on the central and peripheral nervous systems as well as on bone integrity. These will be discussed individually in more detail below.

Paraneoplastic Effects

Paraneoplastic syndromes result from substances formed by the tumor or autoantibodies produced by the body in response to the tumor. They are overall quite rare, but are seen more commonly in some specific cancers (i.e., small cell lung cancer). These phenomena may actually be the first or most prominent manifestation of a malignancy or its recurrence. Many systems can be affected including neuromuscular, musculoskeletal, and metabolic pathways. Hypercalcemia, for example, results when parathyroid hormone-related peptide released by the tumor binds to receptors as parathyroid hormone, resulting in increased bone resorption of calcium from bone and kidney. The syndrome of inappropriate antidiuretic hormone (SIADH) is common but is usually clinically asymptomatic. Cushing’s syndrome results from hypersecretion of adrenocorticotrophic hormone (ACTH). Hematologic and prothrombotic phenomenon can result in anemias or preponderance for thromboembolisms. Paraneoplastic neurologic syndromes are likely autoimmune phenomena. These include Lambert-Eaton myasthenic syndrome, polyneuropathies, and encephalopathies^5,6 (Table 98–1).

Chemotherapy

Chemotherapy is, and likely will continue to be, a cornerstone of cancer treatment. It is given either with intent to cure or prolong life. The myriad complications caused by the ever growing and evolving number and combinations of chemotherapeutic agents available are beyond the scope of this chapter. Many of the agents that cause specific impairments that are of clinical interest to the physiatrist are discussed in detail in the subsequent sections. Generally speaking, however, common complications impacting rehabilitation can include anemia, neutropenia, thrombocytopenia, myopathy, cardiomyopathy, neuropathy, contracture, fatigue, thromboembolism, nausea, and edema, among others.

Radiotherapy

About one-half of all cancer patients will be treated with radiation therapy and it is said to play a critical role in as many as one-quarter of all cancer cures.⁷ The primary goal of radiation therapy in cancer treatments is to kill rapidly growing cancer cells, and to spare slower growing noncancerous cells.

Radiation dosage is determined in part by the inherent radiosensitivity of the organ (Table 98–2), but is also determined by other factors such as patient age, body mass, and comorbidities. Despite its potential lifesaving contribution to cancer survival, it is the adverse effects on surrounding healthy tissues that ultimately become a major source of disability for both patients with active cancer and cancer survivors.⁸ Evaluation and treatment of the long-term complications of radiation are a critically important component in the practice of a cancer rehabilitation specialist and, as such, will be discussed in detail below.

Surgery

Surgery is a mainstay of cancer treatment. Postsurgical impairments are common in the cancer setting as surgeries may compromise the nerves, muscles, bone, and lymphatics, thereby heavily impacting rehabilitation needs. Impairments may be related to the anatomic site, as in the case of a hemipelvectomy where multiple critical structures are resected or compromised. Impairments may also be more systemic, such as diminished stamina following prolonged bedrest. The postsurgical rehabilitation needs of any given individual are unique.

Thromboembolism

Patients with cancer-associated thrombosis (CAT), including deep vein thrombosis (DVT) and pulmonary embolism (PE), carry a higher risk of recurrence, bleeding, and mortality as compared with noncancer patients. In fact, cancer patients are at a four-to-sevenfold higher risk of developing a thrombosis and venous thromboembolisms are the second leading cause of death.⁹ The cause is thought to be activation of the coagulation cascade by the release of proinflammatory and other cytokines, as well as more direct effects including activation of endothelial cells, leukocytes, and platelets themselves.¹⁰

There is a growing consensus that early mobilization for patients with DVT or PE is safe once anticoagulation has begun, and may even be beneficial. This disputes the previous practice recommendations that suggested bedrest as early management of a thrombosis.^11–17 Upper extremity DVT (UEDVT) represents approximately 10% of DVTs and can be idiopathic, but is more often associated with central venous catheter use, pacemakers, or cancer.¹⁸ Although these may also result in PEs, how often this occurs in various settings and what rehabilitation interventions are safe in this situation are largely unknown. For the cancer patient, specifically, this creates a challenge in performing a risk/benefit analysis regarding treatment for upper extremity swelling disorders such as lymphedema. The rehabilitation team may be understandably apprehensive performing decongestive therapy (massage, wrapping, pumps) for a patient with an UEDVT. To support decision-making for therapeutic intervention in patients with a thromboembolism, general guidelines have been developed at Memorial Sloan Kettering Cancer Center and are outlined in Table 98–3.¹⁹ Note that each patient and situation is unique and that these recommendations should never supersede clinical judgment and assessment of the risks and benefits to the patient.

Cancer-Related Fatigue

Cancer-related fatigue (CRF) is its own entity and differs from general fatigue. It is a subjective sense of tiredness or exhaustion that is pervasive and interferes with daily activities, is not proportional to exertion, and is often not relieved by rest.²⁰ It may persist for months or years after successful treatment completion. It is believed to be the most frequent complaint in cancer patients, with an estimated prevalence of 60% to 90%.²¹ Due to this extremely high prevalence, it is prudent for oncology providers to screen patients initially, throughout their cancer treatments, and on subsequent visits.

The etiology of CRF is poorly understood but is most certainly multifactorial. Proinflammatory cytokines, impaired neuroendocrine regulation, and sleep-wake disturbances are some examples of proposed mechanisms.²² Identification and treatment of the multiple comorbidities contributing to CRF is a key initial strategy and includes screening for anemia, thyroid dysfunction, cardiac insufficiency, infections, medication side effects, and mood disorders.

The treatment for CRF that is best supported is aerobic exercise. While it seems counterintuitive to recommend exercise to a fatigued patient, studies have shown that patient compliance is good, particularly with supervised exercise sessions and home-based walking programs.²³ The types of exercises recommended vary, but most evidence points to moderate intensity aerobic exercise with some evidence for resistance training.²⁴ Other nonpharmacological interventions include cognitive-behavioral therapy, patient education, and energy conservation strategies as taught by physical or occupational therapists. Pharmacological interventions are a last resort, and include modafinil and methylphenidate.^25,26 There is preliminary data that anti-proinflammatory cytokine therapies may be effective as well, representing an exciting new therapeutic option for this pervasive and debilitating complication of cancer and cancer treatment.²⁷

Other Medical Complications

Strategies to mitigate medical complications encountered while rehabilitating cancer patients has a limited evidence base. As such, guidelines used in the noncancer population have been adapted to those with cancer. Examples include thrombocytopenia, anemia, neutropenia, cardiac dysfunction, pulmonary dysfunction, and electrolyte abnormalities. Recommended exercise precautions are presented in Table 98–4.¹⁹ As with any intervention, exercise therapy must be prescribed carefully, balancing the risks and benefits.

Brain Dysfunction

Brain dysfunction can result from direct insult by a primary tumor or metastasis, secondary to cancer treatments such as radiation or surgery, or from a paraneoplastic phenomenon.

Brain tumors vary widely in aggressiveness and prognosis. Even a benign or relatively low-grade lesion may have severe functional consequences if in a critical location. In the general population, primary brain tumors are more than twice as likely to be benign than malignant. Primary brain tumors are the most common solid tumor found in children, although in this population, malignant tumors are more common than benign.²⁸ Brain metastases are about ten times more common than a primary brain tumor. Primary cancers of lung, breast, and melanoma comprise nearly 80% of all cases of brain metastasis, with colon and kidney also being common.²⁹

The vast majority of patients with brain tumors of any type will require rehabilitative intervention, so gaining an understanding of this population is imperative. The most common neurologic deficits in brain tumor patients undergoing acute rehabilitation include impaired cognition (80%), weakness (78%), and visual-perceptual impairment (53%). Most patients present with more than one impairment.³⁰

Treatment is largely impairment-based and uses an individualized interdisciplinary approach. Many interventions for these patients are generally similar to those employed for stroke or brain injured patients. Studies of inpatient rehabilitation have consistently shown comparable functional improvement in patients with brain tumors as those with traditional traumatic brain injury or stroke patients. Rates of discharge to the community and lengths of stay are similar or better, although some studies have revealed a higher rate of return to acute care.^28,31–33

Surgery may include partial or complete resection of the tumor. Radiation and chemotherapy are common treatments. All treatments may result in their own set of impairments that range from the acute and self-limiting to the life-long. For example, acute radiation encephalopathy occurs days to weeks following treatment and may be seen during the acute rehabilitation stay. Headaches, lethargy, and worsening of any focal symptoms are common and may respond well to steroids. Between 1 and 6 months, a somnolence syndrome may be seen. This phenomenon is due to demyelination injury to the oligodendrocytes and may also respond to steroids.

Brain tumor survivors often manifest chronic cognitive changes and may be candidates for cognitive rehabilitation interventions both acutely as well as throughout the life course.²⁸ Colloquially referred to as “chemo brain,” cancer-related cognitive impairment often results in deficits of attention, memory, and executive function. Studies show 15% to 61% of patients report this issue. Proposed mechanisms include a systemic inflammatory response as part of the pathophysiology of malignancy and/or inadequate DNA repair mechanisms. Promising treatments requiring further research include modafinil, cognitive rehabilitation, exercise, and diet modifications.³⁴

Spinal Cord Dysfunction

Spinal cord dysfunction can occur secondary to the mass effect of a tumor, which can be either primary or metastatic, or as a result of cancer treatments including radiation or surgery. Other causes in the cancer setting may include infection such as an abscess in the therapeutically immunocompromised, or hemorrhage or infarcts from altered clotting disorders. Regardless of the cause, these patients represent a particularly complex population, often with high-level rehabilitative needs.³⁵

Spinal cord tumors are traditionally categorized into three groups based on the location: extradural (also known as epidural disease), intradural extramedullary, and intradural intramedullary (see Fig. 98–2).

Both primary and metastatic tumors can be seen in each of these locations. Extradural (epidural) tumors are located outside the dura mater. They can originate from the vertebral body, paravertebral space, or traverse the neural foramen to compress the spinal cord. They are also most frequently found in the thoracic spine but are common in all spinal segments. Intradural extramedullary tumors are located within the dura mater but outside the cord parenchyma. Primary intradural extramedullary tumors can arise from peripheral nerves, nerve sheaths, and sympathetic ganglia. Primary lesions in this space are generally benign, but mass effect can cause myelopathy, ischemia, or subarachnoid hemorrhages. Metastases to the intradural extramedullary space are termed leptomeningeal metastases and confer a poor prognosis. Intradural intramedullary tumors are those located within the cord parenchyma. Primary intradural intramedullary tumors arise from neuronal cells and are generally benign. Metastatic lesions are usually found in the setting of already widespread metastatic disease.³⁶

Rehabilitation for patients with malignant spinal cord compression is generally best if begun early and limited in duration. This is due to the fact that patients with cancer generally develop spinal cord dysfunction later in the course of their cancer and often have many other medical comorbidities limiting their prognosis. The degree of functional recovery in these patients can be expected to be less than those of the traditional noncancer spinal cord injury patient. However, function and quality of life can still be improved, including gains in mobility and self-care.^37,38

The Peripheral Nervous System

The peripheral nervous system comprises the nerve roots exiting the spinal cord and include motor, sensory, and autonomic nerves. In the setting of cancer, all of these can be affected. While radiculopathies and brachial plexopathies are seen with some frequency, by far the most common neuropathy is chemotherapy-induced peripheral neuropathy (CIPN).

CIPN is a dose-dependent adverse effect of several antineoplastic agents. It is a major cause of ongoing pain in cancer patients. Generally, it presents in a distal, symmetric, sensory greater than motor, axonal peripheral neuropathy. Clinically the patient reports symptoms in a stocking-and-glove distribution, although autonomic effects and gait abnormalities are possible in more severe cases.³⁹ The highest incidences are with chemotherapy cocktails that include platinum drugs (i.e., cisplatin), vinca alkaloids (i.e., vincristine), and the taxanes (i.e., paclitaxel), among others (Table 98–5). The pathogenesis and degree of toxicities to the nerves, of course, vary by agent. Risk factors include previous neuropathy (i.e., diabetes, alcoholism), higher doses, and longer duration of therapy.⁴⁰ There is currently no prophylactic measure, although research is ongoing.